Researchers have succeeded in switching off, one by one, almost 18,000 genes - 90% of the entire human genome - to find the genes that are essential for cell survival. This finding provides understanding of how our genome works and which genes are crucial in disease like cancer. The study conducted by a team of Toronto researchers, led by Professor Jason Moffat from the University of Toronto's Donnelly Center, with a contribution from Stephane Angers from the Faculty of Pharmacy, was published in Cell on November 25, 2015. It revealed a 'core' set of more than 1,500 essential genes. This lays the foundation for reaching the long-standing goal in biomedical research of pinpointing a role for every single gene in the genome.
‘By turning 90% genes off in different cancer cell lines, the research team uncovered that each tumor relies on a unique set of genes that can be targeted by specific drugs. This finding raises hope of devising new treatments that would target only cancer cells, and leave the surrounding healthy tissue unharmed.’
By turning genes off in five different cancer cell lines, including brain, retinal, ovarian, and two kinds of colorectal cancer cells, the team uncovered that each tumor relies on a unique set of genes that can be targeted by specific drugs. The finding raises hope of devising new treatments that would target only cancer cells, leaving the surrounding healthy tissue unharmed. Moffat, who is also a professor in the Department of Molecular Genetics and a Senior Fellow at the Canadian Institute For Advanced Research (CIFAR), said, "It's when you get outside the core set of essential genes, that it starts to get interesting in terms of how to target particular genes in different cancers and other disease states."
Sequencing of the human genome 12 years ago allowed scientists to compile a list of parts - our 20,000 genes - that make up our cells and bodies. Despite this major achievement, we still didn't understand the function of each gene, or how some genes make us sick when they go wrong. To do this, scientists realized they would have to switch genes off, one by one across the entire genome to determine what processes go wrong in the cells. But the available tools were either inaccurate or too slow.
The recent arrival of the gene editing technology CRISPR has finally made it possible to turn genes off, swiftly and with pinpoint accuracy, kicking off a global race among multiple competing research teams. The Toronto study, along with the paper from Harvard and MIT, published recently in Science, found that roughly 10% of our genes are essential for cell survival.
These findings show the majority of human genes play more subtle roles in the cell because switching them off doesn't kill the cell. But if two or more of such genes are mutated at the same time, or the cells are under environmental stress, their loss begins to count.
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Moffat said, "We can now interrogate our genome at unprecedented resolution in human cells that we grow in the lab with incredible speed and accuracy. In short order, this will lead to a functional map of cancer that will link drug targets to DNA sequence variation."
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Aaron Schimmer, a professor in the Department of Medical Biophysics and a medical oncologist at Princess Margaret Cancer Center, who was not involved in the study, said, "The Moffat group has developed a powerful CRISPR library that could be used by investigators around the world to identify new treatment strategies for the treatment of cancer. I would be interested in using this tool to identify new treatment approaches for acute myeloid leukemia - a blood cancer with a high mortality rate."
Source-Eurekalert